Mesenteric Lymph Duct Ligation Improves Survival in a Lethal Shock Model

Abstract

The goal of this study was to test the hypothesis that factors released from the gut and carried in the mesenteric lymph contribute to mortality in a lethal gut I/R model. To test this hypothesis, a lethal splanchnic artery occlusion (SAO) shock model was used in male Sprague-Dawley rats. In the first set of experiments, ligation of the mesenteric lymph duct (LDL), which prevents gut-derived factors carried in the intestinal lymphatics from reaching the systemic circulation, significantly improved 24-h survival after a 20-min SAO insult (0% vs. 60% survival; P < 0.05). This increase in survival in the LDL-treated rats was associated with a blunted hypotensive response. Because increased iNOS-induced NO levels have been implicated in SAO-induced shock, we measured plasma nitrite/nitrate levels and liver iNOS protein levels in a second group of animals. Ligation of the mesenteric lymph duct significantly abrogated the SAO-induced increase in plasma nitrite/nitrate levels and the induction of hepatic iNOS (P < 0.05). In an additional series of studies, we documented that LDL increased not only 24-h but also long-term 7-day survival. During the course of these studies, we made the unexpected finding that Sprague-Dawley rats from different animal vendors had differential resistance to SAO, and that the time of the year that the experiments were carried out also influenced the results. Nonetheless, in conclusion, these studies support the hypothesis that factors carried in the mesenteric lymph significantly contribute to the development of irreversible shock after SAO.

A “Clean Case” of Systemic Injury

“…PSML has also been demonstrated to enhance leukocyte sequestration as elaborated by up-regulation of both neutrophil and endothelial cell adhesion molecules (18-20). Moreover, cross-transfusion of PSML into naïve rats elicited acute lung injury without the presence of T/HS (11), while mesenteric duct ligation prior to T/HS mitigated this injury (14, 18, 21). …”

Diagnosis biomarkers in acute intestinal ischemic injury: so close, yet so far

“…In the "three hits model", Deitch [23] added the phenomenon of reperfusion injury. In the "gut-lymph" theory, bacteria, cellular components, immune cells, cytokines and chemokines generated by the injured gut travel via the lymphatics to reach the pulmonary circulation, activating alveolar macrophages and contributing to acute lung injury, acute respiratory distress syndrome and multi-organ failure related to AMI [15,16,24].…”

Modulation of Mesenteric Lymph Flow and Composition by Direct Peritoneal Resuscitation From Hemorrhagic Shock

“…Expression of CD11b and lung permeability was 2-fold greater in animals given lipopolysaccharide compared with lipopolysaccharide with mesenteric lymph duct ligation. 26 Other studies 27 with splanchnic artery occlusion and mesenteric lymph duct ligation show a similar role for lymph ducts. Taken together, it appears that the interstitial fluid compartment is the primary conduit for gut-derived inflammatory mediators after hemorrhagic shock and resuscitation.…”